Subscribe to RSS
Early Rhythm Control and the Risks of Ischemic Stroke, Heart Failure, Mortality, and Adverse Events When Performed Early (<3 Months): A Nationwide Cohort Study of Newly Diagnosed Patients with Atrial FibrillationFunding This work was supported in part by grants from the Ministry of Science and Technology (MOST 107-2314-B-075-062-MY3), Taipei Veterans General Hospital (V108B-015, V108B-027, V108C-090, V109C-042, V109C-186), Research Foundation of Cardiovascular Medicine, and Szu-Yuan Research Foundation of Internal Medicine, Taipei, Taiwan.
Background In the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4), early rhythm control was associated with better clinical outcomes for patients with atrial fibrillation (AF). However, the intervention arm had more structured and regular follow-up, and whether the better outcomes of patients assigned to rhythm control were solely due to “early” intervention or because of more regular and structured follow-up was unclear.
Objective In the present study, we aimed to investigate whether the findings of the EAST trial are applicable to the “real-world” clinical setting, where a less structured management protocol is operated.
Methods From 2001 to 2016, 301,064 newly diagnosed AF patients were identified from Taiwan National Health Insurance Research Database. Among these patients, 62,649 AF patients receiving antiarrhythmic drugs or catheter ablation within 1 year after AF being diagnosed (similar to the timing definition of the EAST-AFNET 4 trial) were categorized as the early rhythm control group, and the remaining 238,415 patients were defined as usual care group. Risks of clinical events were compared between the two groups.
Results Compared with usual care, early rhythm control was associated with a lower adjusted risk of ischemic stroke (adjusted hazard ratio [aHR]: 0.771, 95% confidence interval [CI]: 0.751–0.792; p < 0.001), heart failure (aHR: 0.851, 95% CI: 0.806–0.899; p < 0.001), acute myocardial infarction (aHR: 0.915, 95% CI: 0.877–0.955; p < 0.001), mortality (aHR: 0.794, 95% CI: 0.782–0.806; p < 0.001), and composite adverse events (aHR: 0.823, 95% CI: 0.813–0.834; p < 0.001). Compared with usual care, the lower risks of ischemic stroke (aHR: 0.746, 95% CI: 0.717–0.775), heart failure (aHR: 0.819, 95% CI: 0.798–0.841), mortality (aHR: 0.777, 95% CI: 0.759–0.795), and composite adverse events (aHR: 0.802, 95% CI: 0.787–0.818) associated with early rhythm control were even more evident when performed early (<3 months) compared to later periods (3–6 months, 7–9 months, and 10–12 months; p int < 0.001). Principal results were generally consistent for majority of subgroups studied and among the cohort after propensity matching.
Conclusion In this nationwide cohort study, early rhythm control therapy was associated with a lower risk of adverse events compared with usual care among patients with early AF. Outcomes were even better with earlier (<3 months) intervention.
* Drs. Chao and Chan contribute equally to this work and are joint first authors.
** Joint senior authors.
Note: The review process for this paper was fully handled by Christian Weber, Editor-in-Chief.
Study concept and design: T.-F.C., G.Y.H.L., S.-A.C. Acquisition of data: T.-J.C., Y.-H.C. Analysis and interpretation of data: T.-F.C., C.-E.C., G.Y.H.L., S.-A.C. Drafting of the manuscript: T.-F.C., G.Y.H.L. Critical revision of the manuscript for important intellectual content: G.Y.H.L., S.-A.C. Statistical analysis: T.-F.C., T.-C.T., J.-N.L. Study supervision: G.Y.H.L., S.-A.C.
This study is based on data from the Health and Welfare Data Science Center (HWDC), Ministry of Health and Welfare (MOHW), Taiwan. The interpretation and conclusions contained herein do not represent those of HWDC, MOHW, Taiwan.
Received: 21 March 2022
Accepted: 22 March 2022
Accepted Manuscript online:
23 March 2022
Article published online:
30 July 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 Chao TF, Liu CJ, Tuan TC. et al. Lifetime risks, projected numbers, and adverse outcomes in asian patients with atrial fibrillation: a report from the taiwan nationwide AF cohort study. Chest 2018; 153 (02) 453-466
- 2 Potpara TS, Lip GYH, Blomstrom-Lundqvist C. et al. The 4S-AF Scheme (Stroke Risk; Symptoms; Severity of Burden; Substrate): a novel approach to in-depth characterization (rather than classification) of atrial fibrillation. Thromb Haemost 2021; 121 (03) 270-278
- 3 Lip GYH. The ABC pathway: an integrated approach to improve AF management. Nat Rev Cardiol 2017; 14 (11) 627-628
- 4 Hindricks G, Potpara T, Dagres N. et al. ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 2020
- 5 Chao TF, Joung B, Takahashi Y. et al. 2021 Focused update consensus guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: executive summary. Thromb Haemost 2022; 122 (01) 20-47
- 6 Wyse DG, Waldo AL, DiMarco JP. et al; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347 (23) 1825-1833
- 7 Van Gelder IC, Hagens VE, Bosker HA. et al; Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002; 347 (23) 1834-1840
- 8 Marrouche NF, Brachmann J, Andresen D. et al; CASTLE-AF Investigators. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med 2018; 378 (05) 417-427
- 9 Kirchhof P, Camm AJ, Goette A. et al; EAST-AFNET 4 Trial Investigators. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med 2020; 383 (14) 1305-1316
- 10 Chao TF, Chiang CE, Liao JN, Chen TJ, Lip GYH, Chen SA. Comparing the effectiveness and safety of nonvitamin K antagonist oral anticoagulants and warfarin in elderly Asian patients with atrial fibrillation: a nationwide cohort study. Chest 2020; 157 (05) 1266-1277
- 11 Chao TF, Lip GYH, Liu CJ. et al. Relationship of aging and incident comorbidities to stroke risk in patients with atrial fibrillation. J Am Coll Cardiol 2018; 71 (02) 122-132
- 12 Chao TF, Lip GYH, Lin YJ. et al. Age threshold for the use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation: insights into the optimal assessment of age and incident comorbidities. Eur Heart J 2019; 40 (19) 1504-1514
- 13 Tsai CT, Liao JN, Chiang CE. et al. Association of ischemic stroke, major bleeding, and other adverse events with warfarin use vs non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation with a history of intracranial hemorrhage. JAMA Netw Open 2020; 3 (06) e206424
- 14 Chang TY, Chan YH, Chiang CE. et al. Risks and outcomes of gastrointestinal malignancies in anticoagulated atrial fibrillation patients experiencing gastrointestinal bleeding: A nationwide cohort study. Heart Rhythm 2020; 17 (10) 1745-1751
- 15 Chang CH, Lee YC, Tsai CT. et al. Continuation of statin therapy and a decreased risk of atrial fibrillation/flutter in patients with and without chronic kidney disease. Atherosclerosis 2014; 232 (01) 224-230
- 16 Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf 2011; 20 (03) 236-242
- 17 Hsieh CY, Chen CH, Li CY, Lai ML. Validating the diagnosis of acute ischemic stroke in a National Health Insurance claims database. J Formos Med Assoc 2015; 114 (03) 254-259
- 18 Lin YS, Chen TH, Chi CC. et al. Different implications of heart failure, ischemic stroke, and mortality between nonvalvular atrial fibrillation and atrial flutter-a view from a national cohort study. J Am Heart Assoc 2017; 6 (07) 6
- 19 Cheng CL, Lee CH, Chen PS, Li YH, Lin SJ, Yang YH. Validation of acute myocardial infarction cases in the national health insurance research database in taiwan. J Epidemiol 2014; 24 (06) 500-507
- 20 Kaplan RM, Koehler J, Ziegler PD, Sarkar S, Zweibel S, Passman RS. Stroke risk as a function of atrial fibrillation duration and CHA2DS2-VASc score. Circulation 2019; 140 (20) 1639-1646
- 21 Sun W, Freedman B, Martinez C, Wallenhorst C, Yan BP. Atrial fibrillation detected by single time-point handheld electrocardiogram screening and the risk of ischemic stroke. Thromb Haemost 2022; 122 (02) 286-294
- 22 Wallenhorst C, Martinez C, Freedman B. Risk of ischemic stroke in asymptomatic atrial fibrillation incidentally detected in primary care compared with other clinical presentations. Thromb Haemost 2022; 122 (02) 277-285
- 23 Wachter R, Freedman B. Subclinical atrial fibrillation and the risk of recurrent ischemic stroke. Thromb Haemost 2021; 121 (06) 697-699
- 24 Guo Y, Lane DA, Wang L. et al; mAF-App II Trial Investigators. Mobile Health technology to improve care for patients with atrial fibrillation. J Am Coll Cardiol 2020; 75 (13) 1523-1534
- 25 Romiti GF, Pastori D, Rivera-Caravaca JM. et al. Adherence to the ‘Atrial Fibrillation Better Care’ pathway in patients with atrial fibrillation: impact on clinical outcomes-a systematic review and meta-analysis of 285,000 patients. Thromb Haemost 2022; 122 (03) 406-414
- 26 Proietti M, Romiti GF, Olshansky B, Lane DA, Lip GYH. Comprehensive management with the ABC (Atrial Fibrillation Better Care) pathway in clinically complex patients with atrial fibrillation: a post hoc ancillary analysis from the AFFIRM trial. J Am Heart Assoc 2020; 9 (10) e014932
- 27 Yao Y, Guo Y, Lip GYH. mAF-App II Trial investigators. The effects of implementing a mobile health-technology supported pathway on atrial fibrillation-related adverse events among patients with multimorbidity: the mAFA-II randomized clinical trial. JAMA Netw Open 2021; 4 (12) e2140071
- 28 Proietti M, Vitolo M, Harrison SL. et al; ESC-EHRA EORP-AF Long-Term General Registry Investigators. Real-world applicability and impact of early rhythm control for European patients with atrial fibrillation: a report from the ESC-EHRA EORP-AF long-term general registry. Clin Res Cardiol 2022; 111 (01) 70-84